Skip to main content
SpringerLink
Log in

Bio-evaluation of doxorubicin (DOX)-incorporated hydroxyapatite (HAp)-chitosan (CS) nanocomposite triggered on osteosarcoma cells

  • Original Research
  • Published:
Advanced Composites and Hybrid Materials Aims and scope Submit manuscript

Abstract

A new strategic nanostructure consisting inorganic–organic combination for cancer dominancy has been successfully developed using doxorubicin (DOX)-assimilated hydroxyapatite (HAp) as filler and chitosan (CS) as matrix by a solution-based chemical method to access a new window in the field of drug delivery systems (DDS). In this research attempt, we have focussed to fetch an anticancer efficacy from a nanoassembly consisting of DOX-coated nanosized HAp and CS. Basically, HAp is a progressive ceramic biomaterial and has been synthesized by a simple in situ precipitation method, in which the reputed anticancer drug DOX was incorporated and the system was further modified by an extensively used polymer CS. CS is an organic polymer that can be obtained from different organic sources, which may provide mechanical strength to the nanocomposite by making interfacial bonding between them. Such a novel nanocomposite has been physicochemically characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and particle size distribution (PSD). Also, the in vitro biocompatible assistance of the synthesized HAp and the anticancer activity of the newly derived nanocomposite were evaluated through a colorimetric assay (MTT assay). HAp remains biocompatible to osteosarcoma cells, whereas the DOX-HAp-CS nanocomposite produces a remarkable cytotoxicity towards cultured osteosarcoma cells. The prepared DOX-HAp-CS nanocomposite may be potentially used as an anticancer agent for osteosarcoma inhibition.

Doxorubicin (DOX)-intercalated hydroxyapatite (HAp)-chitosan (CS) nanocomposite can be triggered on osteosarcoma cells

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Sumathra M, Rajan M, Munusamy MA (2018) Phosphorylated chitosan armed hydroxyapatite nanocomposite for advancing activity on osteoblast and osteosarcoma cells. New J Chem 42:12457–12466

    CAS  Google Scholar 

  2. Ghosh S, Ghosh S, Jana SK, Pramanik N (2020) Biomedical application of doxorubicin coated hydroxyapatite—poly(lactide-co-glycolide) nanocomposite for controlling osteosarcoma therapeutics. J Nanosci Nanotechnol 20:3994–4004

    Google Scholar 

  3. Aval NA, Islamian JP, Hatamian M, Arabfirouzjaei M, Javadpour, Rashidi M-R (2016) Doxorubicin loaded large-pore mesoporous hydroxyapatite coated superparamagnetic Fe3O4 nanoparticles for cancer treatment. Int J Pharm 509:159–167

    Google Scholar 

  4. Pramanik N, Mohapatra S, Pramanik P (2007) Processing and properties of nano-hydroxyapatite (n-HAp)/poly (ethylene-co-acrylic acid) (EAA) composite using a phosphonic acid coupling agent for orthopedic applications. J Am Ceram Soc 90:369–375

    CAS  Google Scholar 

  5. Pazourková L, Martynková GS, Plachá D (2015) Preparation and mechanical properties of polymeric nanocomposites with hydroxyapatite and hydroxyapatite/clay mineral fillers – review. J Nanotechnol Nanomed Nanobiotechnol 2:2–8

    Google Scholar 

  6. Pramanik N, Biswas SK, Pramanik P (2008) Synthesis and characterization of hydroxyapatite/ poly (vinyl alcohol phosphate) nanocomposite biomaterials. Int J Appl Ceram Technol 5:20–28

    CAS  Google Scholar 

  7. Ghosh S, Raju RSK, Ghosh N, Chaudhury K, Ghosh S, Banerjee I, Pramanik N (2019) Development and physicochemical characterization of doxorubicin encapsulated hydroxyapatite polyvinyl alcohol nanocomposite for repair of osteosarcoma affected bone tissues. C R Chimie 22:46–57

    CAS  Google Scholar 

  8. Pramanik N, Tarafdar A, Pramanik P (2007) Capping agent-assisted synthesis of nanosized hydroxyapatite: comparative studies of their physicochemical properties. J Mater Process Technol 184:131–138

    CAS  Google Scholar 

  9. Ghosh S, Ghosh S, Atta AK, Pramanik N (2018) A succinct overview of hydroxyapatite based nanocomposite biomaterials: fabrications, physicochemical properties and some relevant biomedical applications. J Bionanosci 12:143–158

    Google Scholar 

  10. Sanchez AG, Prokhorov E, Barcenas GL et al (2018) Chitosan-hydroxyapatite nanocomposites: effect of interfacial layer on mechanical and dielectric properties. Mater Chem Phys 217:151–159

    Google Scholar 

  11. Pramanik N, Mishra D, Banerjee I, Maiti TK, Bhargava P, Pramanik P (2008) Chemical synthesis, characterization, and biocompatibility study of hydroxyapatite/chitosan phosphate nanocomposite for bone tissue engineering applications. Int J Biomater 2009:1–8

    Google Scholar 

  12. Hu X, Tao N, Wang X, Xiao J, Wang M (2016) Marine-derived bioactive compounds with anti-obesity effect: a review. J Funct Foods 21:372–387

    CAS  Google Scholar 

  13. Jin Q, Yu H, Wang X, Li K, Li P (2017) Effect of the molecular weight of water-soluble chitosan on its fat-/cholesterol-binding capacities and inhibitory activities to pancreatic lipase. Peerj 5:1–22

    Google Scholar 

  14. Nikpour MR, Rabiee SM, Jahanshahi M (2012) Synthesis and characterization of hydroxyapatite/chitosan nanocomposite materials for medical engineering applications. Compos Part B 43:1881–1886

    CAS  Google Scholar 

  15. Nazeer MA, Yilgor E, Yilgor I (2017) Intercalated chitosan/hydroxyapatite nanocomposites: promising materials for bone tissue engineering applications. Carbohydr Polym 175:38–46

    CAS  Google Scholar 

  16. Thorn CF, Oshiro C, Marsh S, Boussard TH, McLeod H, Klein TE, Altman RB (2011) Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics 21:440–446

    CAS  Google Scholar 

  17. Armstrong J, Dass CR (2018) Doxorubicin action on mitochondria: relevance to osteosarcoma therapy? Curr Drug Targets 19:432–438

    CAS  Google Scholar 

  18. Mohammadi ZA, Aghamiri SF, Zarrabi A, Talaie MR (2015) A comparative study on non-covalent functionalization of carbonnanotubes by chitosan and its derivatives for delivery of doxorubicin. Chem Phys Lett 642:22–28

    Google Scholar 

  19. Sukhodub LB, Yanovska GO, Kuznetsov VM, Martynyuk OO, Sukhodub LF (2016) Injectable biopolymer-hydroxyapatite hydrogels: obtaining and their characterization. J Nano Electron Phys 8:01032–01040

    Google Scholar 

  20. Jayaweera HDAC, Siriwardane I, de Silva KMN, de Silva RM (2018) Synthesis of multifunctional activated carbon nanocomposite comprising biocompatible flake nano hydroxyapatite and natural turmeric extract for the removal of bacteria and lead ions from aqueous solution. Chem Cent J 12:1–14

    Google Scholar 

  21. Pramanik N, Mohapatra S, Bhargava P, Pramanik P (2009) Chemical synthesis and characterization of hydroxyapatite (HAp)-poly (ethylene co vinyl alcohol) (EVA) nanocomposite using a phosphonic acid coupling agent for orthopedic applications. Mater Sci Eng C 29:228–236

    CAS  Google Scholar 

  22. Maheshwari SU, Samuel VK, Nagiah N (2014) Fabrication and evaluation of (PVA/HAp/PCL) bilayer composites as potential scaffolds for bone tissue regeneration application. Ceram Int 40:8469–8477

    Google Scholar 

  23. Plowright R, Belton DJ, Kaplan DL, Perry CC (2017) Quantifying the efficiency of hydroxyapatite mineralising peptides. Sci Rep 7:7681–7690

    Google Scholar 

  24. Manoj M, Mangalaraj D, Ponpandian N, Viswanathan C (2015) Core–shell hydroxyapatite/Mg nanostructures: surfactant free facile synthesis, characterization and their in vitro cell viability studies against leukaemia cancer cells (K562). RSC Adv 5:48705–48711

    CAS  Google Scholar 

  25. Poinern GJE, Brundavanam R, Le XT, Djordjevic S, Prokic M, Fawcett D (2011) Thermal and ultrasonic influence in the formation of nanometer scale hydroxyapatite bio-ceramic. Int J Nanomedicine 6:2083–2095

    CAS  Google Scholar 

  26. Garskaite E, Gross K-A, Yang S-W, Yang TC-K, Yang J-C, Kareiva A (2014) Effect of processing conditions on the crystallinity and structure of carbonated calcium hydroxyapatite (CHAp). Cryst Eng Comm 16:3950–3959

    CAS  Google Scholar 

  27. Krishnamoorthy LP, Moorthy RK, Umapathy D, Kannan MK, Ganesan N, Arockiam AJV (2017) Encapsulation of doxorubicin in PLGA nanoparticles enhances cancer therapy. Clin Oncol 2:1–6

    Google Scholar 

  28. Li J-M, Zhang W, Su H, Wang Y-Y, Tan C-P, Ji L-N, Mao Z-W (2015) Reversal of multidrug resistance in MCF-7/ Adr cells by codelivery of doxorubicin and BCL2 siRNA using a folic acid-conjugated polyethylenimine hydroxypropyl-β-cyclodextrin nanocarrier. Int J Nanomedicine 10:3147–3162

    CAS  Google Scholar 

  29. Kayal S, Ramanujan RV (2010) Doxorubicin loaded PVA coated iron oxide nanoparticles for targeted drug delivery. Mater Sci Eng C 30:484–490

    CAS  Google Scholar 

  30. Wang Z, Yan Y, Shen X, Qian T, Wang J, Sun Q, Jin C (2018) Lignocellulose-chitosan-multiwalled carbon nanotube composites with improved mechanical strength, dimensional stability and fire retardancy. Polymers 10:341–355

    Google Scholar 

  31. Samandari SS, Yekta H, Samandari SS (2015) Effect of iron substitution in hydroxyapatite matrix on swelling properties of composite bead. J Miner Met Mater Eng 1:19–25

    Google Scholar 

  32. Silva ATB, Coelho AG, Lopes LC d S, MVA M, Crespilho FN, Merkoçi A, da Silva WC (2013) Nano-assembled supramolecular films from chitosan-stabilized gold nanoparticles and cobalt (II) phthalocyanine. J Braz Chem Soc 24:1237–1245

    CAS  Google Scholar 

  33. Mansur HS, Mansur AAP, Curti E, Almeida MVD (2013) Functionalized-chitosan/quantum dot nano-hybrids for nanomedicine applications: towards biolabeling and biosorbing phosphate metabolites. J Mater Chem B 1:1696–1711

    CAS  Google Scholar 

  34. Yuan Q, Shah J, Hein S, Misra RDK (2010) Controlled and extended drug release behavior of chitosan-based nanoparticle carrier. Acta Biomater 6:1140–1148

    CAS  Google Scholar 

  35. Degirmenbasi N, Kalyon DM, Birinci E (2006) Biocomposites of nanohydroxyapatite with collagen and poly (vinyl alcohol). Colloids Surf. B: Biointerfaces 48:42–49

  36. Pramanik N, Imae T (2012) Fabrication and characterization of dendrimer-functionalized mesoporous hydroxyapatite. Langmuir 28:14018–14027

    CAS  Google Scholar 

  37. Dadsetan M, Taylora KE, Yong C, Bajzer Ž, Lu L, Yaszemski MJ (2019) Controlled release of doxorubicin from pH-responsive microgels. Acta Biomater 9:5438–5446

    Google Scholar 

  38. Pelss J, Loca D, Cimdina LB, Locs J, Lakevics V (2011) Release of anticancer drug doxorubicin from biodegradable polymer coated porous hydroxyapatite scaffolds. Adv Mater Res 284-286:1770–1773

    CAS  Google Scholar 

  39. You J-O, Guo P, Auguste DT (2013) A multi-targeted drug delivery vehicle approach that targets, triggers, and thermally ablates HER2+ breast cancer cells. Angew Chem Int Ed Eng 52:4141–4146

    CAS  Google Scholar 

  40. Jadalannagari S, Deshmukh K, Ramanan SR, Kowshik M (2014) Antimicrobial activity of hemocompatible silver doped hydroxyapatite nanoparticles synthesized by modified sol–gel technique. Appl Nanosci 4:133–141

    CAS  Google Scholar 

  41. Cai Y, Liu Y, Yan W et al (2007) Role of hydroxyapatite nanoparticle size in bone cell proliferation. J Mater Chem 17:3780–3787

    CAS  Google Scholar 

  42. Zheng F, Wang S, Shen M, Zhub M, Shi X (2013) Antitumor efficacy of doxorubicin-loaded electrospun nano-hydroxyapatite–poly (lactic-co-glycolic acid) composite nanofibers. Polym Chem 4:933–941

    CAS  Google Scholar 

  43. Amin A, Kandil H, Awad HM, Ismail MN (2015) Preparation and characterization of chitosan–hydroxyapatite–glycopolymer/Cloisite 30 B nanocomposite for biomedical applications. Polym Bull 72(6):1497–1513

    CAS  Google Scholar 

  44. Qi L-F, Xu Z-R, Li Y, Jiang X, Han X-Y (2005) In vitro effects of chitosan nanoparticles on proliferation of human gastric carcinoma cell line MGC803 cells. World J Gastroenterol 11:5136–5141

    CAS  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledged the Indian Institute of Technology (IIT), Kharagpur, for providing experimental facilities and the National Institute of Technology (NIT), Arunachal Pradesh, India, for other assistance.

Funding

This study received financial support from Indian Council of Medical Research (ICMR), New Delhi (Project Grant No. 5/7/1263/2015-CH), Seed Research Grant under TEQIP-III (Grant No. NIT-AP/TEQIP-III/Seed Grant/BAS(CHEM)/NP/2019 Dated 4/9/2019) National Institute of Technology (NIT), Arunachal Pradesh and Collaborative Research Scheme Project, MHRD, New Delhi (ID: 1-5726236331).

Author information

Authors and Affiliations

  1. Department of Chemistry, National Institute of Technology, Arunachal Pradesh, Yupia, 791112, India

    Saikat Ghosh & Nabakumar Pramanik

  2. Department of Chemistry, Nalanda College of Engineering, Nalanda, Bihar, 803108, India

    Sampad Ghosh

Authors
  1. Saikat Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sampad Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nabakumar Pramanik
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conception: Nabakumar Pramanik

Experimental design: Nabakumar Pramanik, Saikat Ghosh, Sampad Ghosh

Carrying out measurements: Saikat Ghosh

Manuscript composition: Sampad Ghosh, Nabakumar Pramanik

Corresponding author

Correspondence to Nabakumar Pramanik.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghosh, S., Ghosh, S. & Pramanik, N. Bio-evaluation of doxorubicin (DOX)-incorporated hydroxyapatite (HAp)-chitosan (CS) nanocomposite triggered on osteosarcoma cells. Adv Compos Hybrid Mater 3, 303–314 (2020). https://doi.org/10.1007/s42114-020-00154-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42114-020-00154-4

Keywords

Search

Navigation